TMC114-TiDP3-C182 - A Study to Compare the Oral Bioavailability of a 800 mg Prototype Tablet Formulation of Darunivar (DRV) to That of the 400 mg Commercial Tablet Formulation in the Presence of Low Dose Ritonavir, Under Fasted and Fed Conditions

The purpose of this study is to compare the drug levels of darunavir obtained after administration of a single administration of the 800 mg tablet (new formulation) to that following administration of two 400 mg commercial tablets formulation when administered under fed and fasted conditions to those also taking low-dose ritonavir. Darunavir is marketed for the treatment of HIV. The short-term safety and tolerability of darunavir following administration of a single 800 mg dose of darunavir given to healthy volunteers taking taking low-dose ritonavir will also be assessed.

A Phase I, Open Label, Randomized, Single Dose, Crossover Study in Healthy Subjects to Compare the Oral Bioavailability of a Prototype Tablet Formulation of Darunavir 800mg(G002) to That of the Commercial 400mg(F030) Tablet Formulation Under Fed & Fasted Conditions, in Presence of Low-dose Ritonavir

Further study details as provided by Tibotec Pharmaceuticals, Ireland:

Primary Outcome Measures:

Plasma levels of DRV 800 mg new formulation compared with 2x400 mg commercial formulation in fed and fasted conditions and in presence of low dose rtv [ Time Frame: Plasma levels of DRV in each session at 15 timepoints and plasma levels of rtv after intake on Day 3 at 13 timepoints ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

The short-term safety and tolerability of darunavir following administration of a single 800 mg dose of darunavir in the presence of low-dose ritonavir [ Time Frame: 9 weeks (this includes treatment, washout and follow up period and is excluding screening period of maximum 21 days before first medication intake) ] [ Designated as safety issue: No ]

DRV commercial formulation/ DRV new formulation/ rtv 100mg tab DRV two 400 mg commercial formulation tablets in the morning of day 3 after food + rtv 100 mg 1/day on Day 1-5 [Treatment A] then after 7 days off treatment start DRV 800 mg new formulation tablet in the morning of Day 3 after food + rtv 100 mg 1/day on Day 1-5 [Treatment B]

Drug: DRV commercial formulation/ DRV new formulation/ rtv 100mg tab

DRV two 400 mg commercial formulation tablets in the morning of day 3 after food + rtv 100 mg 1/day on Day 1-5 [Treatment A], then after 7 days off treatment start DRV 800 mg new formulation tablet in the morning of Day 3 after food + rtv 100 mg 1/day on Day 1-5 [Treatment B]

Experimental: 2

DRV commercial formulation/ DRV new formulation/ rtv 100mg tab DRV 800 mg new formulation tablet/rtv 100mg tablet in the morning of Day 3 after food+ rtv 100 mg 1/day on Day 1-5 [Treatment B] then after 7 days off treatment start DRV two 400 mg commercial formulation tablets in the morning of day 3 after food + rtv 100 mg 1/day on Day 1-5 [Treatment A]

Drug: DRV commercial formulation/ DRV new formulation/ rtv 100mg tab

DRV 800 mg new formulation tablet/rtv 100mg tablet in the morning of Day 3 after food+ rtv 100 mg 1/day on Day 1-5 [Treatment B], then after 7 days off treatment start DRV two 400 mg commercial formulation tablets in the morning of day 3 after food + rtv 100 mg 1/day on Day 1-5 [Treatment A]

Experimental: 3

DRV commercial formulation/ DRV new formulation/ rtv 100mg tab DRV two 400 mg commercial formulation tablets in the morning of day 3 fasting + rtv 100 mg 1/day on Day 1-5 [Treatment C] then after 7 days off treatment start DRV 800 mg new formulation in the morning of day 3 fasting + rtv 100 mg 1/day on Day 1-5 [Treatment D]

Drug: DRV commercial formulation/ DRV new formulation/ rtv 100mg tab

DRV two 400 mg commercial formulation tablets in the morning of day 3 fasting + rtv 100 mg 1/day on Day 1-5 [Treatment C], then after 7 days off treatment start DRV 800 mg new formulation in the morning of day 3 fasting + rtv 100 mg 1/day on Day 1-5 [Treatment D]

Experimental: 4

DRV commercial formulation/ DRV new formulation/ rtv 100mg tab DRV 800 mg new formulation in the morning of day 3 fasting + rtv 100 mg 1/day on Day 1-5 [Treatment D] then after 7 days off treatment start DRV two 400 mg commercial formulation tablets in the morning of day 3 fasting + rtv 100 mg 1/day on Day 1-5 [Treatment C]

Drug: DRV commercial formulation/ DRV new formulation/ rtv 100mg tab

DRV 800 mg new formulation in the morning of day 3 fasting + rtv 100 mg 1/day on Day 1-5 [Treatment D], then after 7 days off treatment start DRV two 400 mg commercial formulation tablets in the morning of day 3 fasting + rtv 100 mg 1/day on Day 1-5 [Treatment C]

Detailed Description:

This is an open label study, which means that all parties including the study doctor, the healthy volunteer and the sponsor will know at all times which treatment group the volunteer is in. This is a cross over trial, which means that every volunteer will be sequentially subjected to 2 different treatments. A total of 32 healthy volunteers will participate in this study. Volunteers will be divided over 2 panels of 16 volunteers each. Volunteers in Panel 1 will be randomly assigned to treatment sequence AB or BA. Volunteers in Panel 2 will be randomly assigned to treatment sequence CD or DC. During all treatment periods 100 mg ritonavir (rtv) will be dosed once daily on Day 1 to Day 5. In treatment A you will receive a single dose of darunavir (DRV) two 400 mg commercial formulation in the morning of day 3 after a standard breakfast. In treatment B you will receive a single dose of darunavir (DRV) 800 mg new formulation in the morning of Day 3 also under fed conditions. In treatment C you will receive a single dose of darunavir (DRV) two 400 mg commercial formulation in the morning of day 3 under fasted conditions. In treatment D you will receive a single dose of darunavir (DRV) 800 mg new formulation in the morning of day 3 also under fasted conditions. Treatment sessions are organized with 7 days between treatment periods. In each session, an extensive investigation of the levels of DRV and rtv in the blood circulation is planned. Levels of DRV will be assessed at 15 different time points, i.e. before administration of DRV 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 24, 48 and 72 hours after intake of DRV. Levels of rtv will be assessed at 13 different time points, i.e. before administration of rtv on Day 3, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9 and 12 hours after intake of rtv on day 3 and before administration of rtv on Day 4. Standard Safety assessments (blood biochemistry and hematology, urine analysis, ECG, pulse rate and blood pressure) will be performed on Day1, 3 and 6 in each Treatment period. Two 400 mg DRV commercial tablet formulation (F030) single dose on Day 3 of treatment A and C; 800 mg DRV new tablet formulation (G002) single dose on Day 3 of treatment B and D; 100 mg rtv capsule once daily on Day 1 to Day 5. All intake are oral.

Eligibility

Ages Eligible for Study:

18 Years to 55 Years

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

Yes

Criteria

Inclusion Criteria:

Non-smoking, or smoking no more than 10 cigarettes, or 2 cigars, or 2 pipes per day for at least 3 months prior to selection

Normal weight as defined by a Body Mass Index (BMI, weight in kg divided by the square of height in meters) of 18.0 to 30.0 kg/m2, extremes included

Use of effective non hormonal birth control methods, or willing to continue practicing these birth control methods for at least 30 days after the end of the treatment period for female volunteers of childbearing potential

Negative serum pregnancy test and will not be breast feeding at screening

Able to comply with protocol requirements

Healthy on the basis of a medical evaluation that reveals the absence of any clinically relevant abnormality and includes a physical examination, medical history, electrocardiogram (ECG), vital signs, and the results of blood biochemistry, blood coagulation, and hematology tests and a urinalysis carried out at screening

Exclusion Criteria:

Positive HIV 1 or HIV 2 test at screening

Hepatitis A, B or C infection at screening

History of significant skin disease such as, but not limited to rash or eruptions, food allergy or psoriasis

Allergy, hypersensitivity or intolerance to DRV and rtv

History of allergy to drugs such as, but not limited to, sulphonamides and penicillins

Contacts and Locations

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Please refer to this study by its ClinicalTrials.gov identifier: NCT01052883